Feliú J E, Hue L, Hers H G
Proc Natl Acad Sci U S A. 1976 Aug;73(8):2762-6. doi: 10.1073/pnas.73.8.2762.
Treatment of isolated rat hepatocytes with saturating concentrations of glucagon caused several modifications properties of pyruvate kinase (ATP:pyruvate 2-O-phosphotransferase, EC 2.7.1.40): S0.5 (substrate concentration at half maximum velocity) for phosphoenolpyruvate was about doubled, whereas Vmax was not changed; the activity measured at 0.15 mM phosphoenolpyruvate (physiological concentration) was reduced 65-80%; and there was also an increase in the Hill coefficient and in the affinity of the enzyme for the inhibitors Mg-ATP and alanine. Glucagon, 3':5'-cyclic AMP, and epinephrine caused an inactivation of pyruvate kinase together with a sitmulation of gluconeogenesis. Insulin (10 nM) antagonized the effect of suboptimal doses of glucagon or cyclic AMP and of even maximal doses of epinephrine, on both pyruvate kinase activity and on gluconeogenesis. These observations can be explained by a phosphorylation of pyruvate kinase by cyclic-AMP-dependent protein kinase, as described by Ljungström et al. [(1974) Biochim. Biophys. Acta 358, 289-298] in a reconstructed system. They offer a molecular explanation for the hormonal control of gluconeogenesis. Glucose caused an inhibition of gluconeogenesis with no corresponding change in pyruvate kinase activity.
用饱和浓度的胰高血糖素处理离体大鼠肝细胞，导致丙酮酸激酶（ATP：丙酮酸2-O-磷酸转移酶，EC 2.7.1.40）的几个特性发生改变：磷酸烯醇丙酮酸的S0.5（最大速度一半时的底物浓度）约增加一倍，而Vmax不变；在0.15 mM磷酸烯醇丙酮酸（生理浓度）下测得的活性降低65 - 80%；并且希尔系数以及酶对抑制剂Mg-ATP和丙氨酸的亲和力也增加。胰高血糖素、3':5'-环磷酸腺苷和肾上腺素导致丙酮酸激酶失活，同时刺激糖异生作用。胰岛素（10 nM）拮抗次优剂量的胰高血糖素或环磷酸腺苷以及甚至最大剂量肾上腺素对丙酮酸激酶活性和糖异生作用的影响。正如Ljungström等人[（1974年）《生物化学与生物物理学报》358，289 - 298]在一个重构系统中所描述的，这些观察结果可以通过环磷酸腺苷依赖性蛋白激酶对丙酮酸激酶的磷酸化来解释。它们为糖异生作用的激素调控提供了分子解释。葡萄糖导致糖异生作用受到抑制，而丙酮酸激酶活性没有相应变化。
